The objectives of this project are to study the effects of several humoral agents and cellular elements on erythropoiesis in culture, to characterize the interactions of these factors with erythropoietin, and to define conditions that optimally induce the increased synthesis of fetal hemoglobin in cultures of human erythroid colonies. Mononuclear cells obtained from the peripheral blood and from marrow aspirates will be plated in plasma clot cultures in the presence of erythropoietin. The proliferation of red cell colonies and the differential synthesis of fetal and adult hemoglobins will be quantified under baseline conditions. Changes in these parameters will be studied in cultures containing agents known to affect the proliferation of erythroia progenitors. The individual actions of these agents and synergism among them will be determined in terms of their effect on the differential synthesis of fetal and adult hemoglobins. An attempt will be made to relate the findings to physiologic mechanisms underlying the modulation of hemoglobin ontogenetic development and to suggest ways to modify this process by pharmacologic intervention.